Advancements in Human Brain Organoid Models: Integrating Multi-Omics and Genetic Engineering to Unravel Neurodevelopmental Disorders
DOI:
https://doi.org/10.58445/rars.3382Keywords:
Brain Organoids, Neurodevelopmental Disorders, Single-Cell Transcriptomics, Multi-Omics Integration, CRISPR-Cas9 Genome Editing, Autism Spectrum Disorder (ASD), Microcephaly, Parkinson’s Disease, Organoid Engineering, Functional MaturationAbstract
Human brain organoids have emerged as transformative tools for modeling early neural development and investigating the molecular basis of neurodevelopmental disorders. Recent advances in stem cell engineering, spatial patterning, and three-dimensional culture have enabled the generation of increasingly complex models that recapitulate features of the embryonic human brain, including region-specific organization, neuronal diversity, and early circuit formation. Simultaneously, the integration of single-cell transcriptomics and multi-omics technologies has enhanced the resolution with which these models can be analyzed, allowing for precise mapping of developmental trajectories and disease-associated perturbations. In parallel, CRISPR-based genome editing has facilitated targeted manipulation of neurodevelopmental genes, enabling mechanistic insights into rare and common disorders such as autism spectrum disorder and microcephaly. This review synthesizes recent progress in the engineering, validation, and application of brain organoid systems, highlighting key studies that combine morphogenetic fidelity with high-throughput genomic and functional analysis. We also discuss current limitations—including variability, incomplete maturation, and ethical considerations—and propose strategies for improving the reproducibility and translational relevance of brain organoids in disease modeling.
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